NZ247791A - Pyrrolothienopyrazine derivatives, their preparation and pharmaceutical compositions - Google Patents

Pyrrolothienopyrazine derivatives, their preparation and pharmaceutical compositions

Info

Publication number: NZ247791A
Authority: NZ; New Zealand
Prior art keywords: formula; compounds; group; thieno; pyrrolo
Prior art date: 1992-06-05

Application number

NZ247791A

Other languages

English (en)

Inventor

Sylvian Rault

Jean-Charles Lancelot

Vicente Juan-Carlos Pilo

Max Robba

Lemaitre Beatrice Guardiola

Pierre Renard

Gerard Adam

Original Assignee

Adir

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1992-06-05

Filing date

1993-06-04

Publication date

1994-12-22

1993-06-04 Application filed by Adir filed Critical Adir

1994-12-22 Publication of NZ247791A publication Critical patent/NZ247791A/en

Links

238000002360 preparation method Methods 0.000 title claims description 25
239000008194 pharmaceutical composition Substances 0.000 title claims description 8
150000001875 compounds Chemical class 0.000 claims abstract description 100
150000003839 salts Chemical class 0.000 claims abstract description 19
239000002253 acid Substances 0.000 claims abstract description 17
230000003287 optical effect Effects 0.000 claims abstract description 11
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 51
-1 alkyl radicals Chemical class 0.000 claims description 43
238000000034 method Methods 0.000 claims description 34
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 26
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 14
239000002904 solvent Substances 0.000 claims description 14
230000008569 process Effects 0.000 claims description 12
GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
239000000203 mixture Substances 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
125000004043 oxo group Chemical group O=* 0.000 claims description 10
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 10
150000001412 amines Chemical class 0.000 claims description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
125000000217 alkyl group Chemical group 0.000 claims description 8
238000001914 filtration Methods 0.000 claims description 7
239000000377 silicon dioxide Substances 0.000 claims description 7
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
125000001309 chloro group Chemical group Cl* 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
238000004587 chromatography analysis Methods 0.000 claims description 5
238000002425 crystallisation Methods 0.000 claims description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
208000035475 disorder Diseases 0.000 claims description 5
238000000605 extraction Methods 0.000 claims description 5
125000000623 heterocyclic group Chemical group 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
238000000746 purification Methods 0.000 claims description 5
239000011347 resin Substances 0.000 claims description 5
229920005989 resin Polymers 0.000 claims description 5
239000005864 Sulphur Substances 0.000 claims description 4
239000004480 active ingredient Substances 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
125000005843 halogen group Chemical group 0.000 claims description 4
230000002140 halogenating effect Effects 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
125000004193 piperazinyl group Chemical group 0.000 claims description 4
230000002265 prevention Effects 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
125000001624 naphthyl group Chemical group 0.000 claims description 3
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
208000007848 Alcoholism Diseases 0.000 claims description 2
208000019901 Anxiety disease Diseases 0.000 claims description 2
208000030814 Eating disease Diseases 0.000 claims description 2
208000019454 Feeding and Eating disease Diseases 0.000 claims description 2
208000026139 Memory disease Diseases 0.000 claims description 2
208000019695 Migraine disease Diseases 0.000 claims description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 2
208000002193 Pain Diseases 0.000 claims description 2
208000028017 Psychotic disease Diseases 0.000 claims description 2
206010047700 Vomiting Diseases 0.000 claims description 2
230000009471 action Effects 0.000 claims description 2
125000002252 acyl group Chemical group 0.000 claims description 2
201000007930 alcohol dependence Diseases 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
230000036506 anxiety Effects 0.000 claims description 2
125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
210000003169 central nervous system Anatomy 0.000 claims description 2
OYQJNUJWLVFCPE-UHFFFAOYSA-N chembl65974 Chemical compound C1CN(C)CCN1C(C1=CC=CN11)=NC2=C1SC=C2 OYQJNUJWLVFCPE-UHFFFAOYSA-N 0.000 claims description 2
125000004663 dialkyl amino group Chemical group 0.000 claims description 2
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 2
235000014632 disordered eating Nutrition 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
230000030136 gastric emptying Effects 0.000 claims description 2
239000001257 hydrogen Substances 0.000 claims description 2
229910052739 hydrogen Inorganic materials 0.000 claims description 2
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
206010027599 migraine Diseases 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
150000004885 piperazines Chemical class 0.000 claims description 2
150000003053 piperidines Chemical class 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
150000003235 pyrrolidines Chemical class 0.000 claims description 2
125000000168 pyrrolyl group Chemical group 0.000 claims description 2
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
201000000980 schizophrenia Diseases 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
230000008673 vomiting Effects 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims 1
239000003814 drug Substances 0.000 abstract 1
238000002844 melting Methods 0.000 description 90
230000008018 melting Effects 0.000 description 90
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
JKUQIELHODAIQH-UHFFFAOYSA-N pyrrolo[1,2-a]thieno[3,2-e]pyrazine Chemical compound N12C=CC=C2C=NC2=C1SC=C2 JKUQIELHODAIQH-UHFFFAOYSA-N 0.000 description 25
230000003595 spectral effect Effects 0.000 description 22
FHIGHEZQZRKYKO-UHFFFAOYSA-N pyrrolo[1,2-a]thieno[2,3-e]pyrazine Chemical compound N12C=CC=C2C=NC2=C1C=CS2 FHIGHEZQZRKYKO-UHFFFAOYSA-N 0.000 description 19
102000035037 5-HT3 receptors Human genes 0.000 description 16
108091005477 5-HT3 receptors Proteins 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
239000000243 solution Substances 0.000 description 14
102000005962 receptors Human genes 0.000 description 13
108020003175 receptors Proteins 0.000 description 13
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
238000001953 recrystallisation Methods 0.000 description 12
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
241000700159 Rattus Species 0.000 description 8
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 8
238000006073 displacement reaction Methods 0.000 description 7
239000003826 tablet Substances 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
150000001540 azides Chemical class 0.000 description 6
230000027455 binding Effects 0.000 description 6
239000002609 medium Substances 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
150000003254 radicals Chemical class 0.000 description 6
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
230000002295 serotoninergic effect Effects 0.000 description 6
GKTQKQTXHNUFSP-UHFFFAOYSA-N thieno[3,4-c]pyrrole-4,6-dione Chemical compound S1C=C2C(=O)NC(=O)C2=C1 GKTQKQTXHNUFSP-UHFFFAOYSA-N 0.000 description 6
GHZGUQPTBSKPOO-UHFFFAOYSA-N 2-pyrrol-1-ylthiophene-3-carbonyl azide Chemical compound C1=CSC(N2C=CC=C2)=C1C(=O)N=[N+]=[N-] GHZGUQPTBSKPOO-UHFFFAOYSA-N 0.000 description 5
RWSVHUMXTCBTBP-UHFFFAOYSA-N 3-pyrrol-1-ylthiophene-2-carbonyl azide Chemical compound S1C=CC(N2C=CC=C2)=C1C(=O)N=[N+]=[N-] RWSVHUMXTCBTBP-UHFFFAOYSA-N 0.000 description 5
150000003857 carboxamides Chemical class 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
238000010992 reflux Methods 0.000 description 5
YJSKZIATOGOJEB-UHFFFAOYSA-N thieno[2,3-b]pyrazine Chemical compound C1=CN=C2SC=CC2=N1 YJSKZIATOGOJEB-UHFFFAOYSA-N 0.000 description 5
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 4
FEROPKNOYKURCJ-UHFFFAOYSA-N 4-amino-N-(1-azabicyclo[2.2.2]octan-3-yl)-5-chloro-2-methoxybenzamide Chemical compound COC1=CC(N)=C(Cl)C=C1C(=O)NC1C(CC2)CCN2C1 FEROPKNOYKURCJ-UHFFFAOYSA-N 0.000 description 4
GEHBXDUPCDPDKS-UHFFFAOYSA-N 4-phenyl-3-pyrrol-1-ylthiophene-2-carbonyl azide Chemical compound [N-]=[N+]=NC(=O)C=1SC=C(C=2C=CC=CC=2)C=1N1C=CC=C1 GEHBXDUPCDPDKS-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
230000035508 accumulation Effects 0.000 description 4
238000009825 accumulation Methods 0.000 description 4
239000000556 agonist Substances 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 4
239000003446 ligand Substances 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
239000000725 suspension Substances 0.000 description 4
229950004681 zacopride Drugs 0.000 description 4
FELGMEQIXOGIFQ-CYBMUJFWSA-N (3r)-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1C[C@@H]1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-CYBMUJFWSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
GEAXLHPORCRESC-UHFFFAOYSA-N chlorocyclohexatriene Chemical class ClC1=CC=C=C[CH]1 GEAXLHPORCRESC-UHFFFAOYSA-N 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000013078 crystal Substances 0.000 description 3
QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 3
238000011534 incubation Methods 0.000 description 3
238000005259 measurement Methods 0.000 description 3
229960005343 ondansetron Drugs 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 3
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
WSCYUZJLJQNLSQ-UHFFFAOYSA-N 3-pyrrol-1-ylthiophene-2-carboxylic acid Chemical compound S1C=CC(N2C=CC=C2)=C1C(=O)O WSCYUZJLJQNLSQ-UHFFFAOYSA-N 0.000 description 2
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
SZCAHTPPBLBGEE-UHFFFAOYSA-N 5-phenyl-2-pyrrol-1-ylthiophene-3-carbonyl azide Chemical compound C1(=CC=CC=C1)C1=CC(=C(S1)N1C=CC=C1)C(=O)N=[N+]=[N-] SZCAHTPPBLBGEE-UHFFFAOYSA-N 0.000 description 2
BTRTUTNEJSIEMN-UHFFFAOYSA-N 8-chloro-3-thia-1,7-diazatricyclo[7.3.0.02,6]dodeca-2(6),4,7,9,11-pentaene Chemical compound N12C=CC=C2C(Cl)=NC2=C1SC=C2 BTRTUTNEJSIEMN-UHFFFAOYSA-N 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
230000001270 agonistic effect Effects 0.000 description 2
230000003042 antagnostic effect Effects 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
208000006218 bradycardia Diseases 0.000 description 2
239000000872 buffer Substances 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
230000000747 cardiac effect Effects 0.000 description 2
239000003610 charcoal Substances 0.000 description 2
UJCWXFPFFHIOCY-UHFFFAOYSA-N chembl66408 Chemical compound C=1C=CC=CC=1CN(CC1)CCN1C(C1=CC=CN1C=1C=2)=NC=1SC=2C1=CC=CC=C1 UJCWXFPFFHIOCY-UHFFFAOYSA-N 0.000 description 2
XVBNTXFFWWXLMY-UHFFFAOYSA-N chembl66540 Chemical compound C=1C=CC=CC=1CN(CC1)CCN1C(C1=CC=CN1C=1S2)=NC=1C=C2C1=CC=CC=C1 XVBNTXFFWWXLMY-UHFFFAOYSA-N 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
230000000694 effects Effects 0.000 description 2
210000005153 frontal cortex Anatomy 0.000 description 2
210000001905 globus pallidus Anatomy 0.000 description 2
210000001320 hippocampus Anatomy 0.000 description 2
239000001863 hydroxypropyl cellulose Substances 0.000 description 2
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
GPKUICFDWYEPTK-UHFFFAOYSA-N methoxycyclohexatriene Chemical class COC1=CC=C=C[CH]1 GPKUICFDWYEPTK-UHFFFAOYSA-N 0.000 description 2
WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical class [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 2
TWEQNZZOOFKOER-UHFFFAOYSA-N methyl 3-aminothiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1N TWEQNZZOOFKOER-UHFFFAOYSA-N 0.000 description 2
210000001577 neostriatum Anatomy 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
239000012071 phase Substances 0.000 description 2
CUQCMXFWIMOWRP-UHFFFAOYSA-N phenyl biguanide Chemical compound NC(N)=NC(N)=NC1=CC=CC=C1 CUQCMXFWIMOWRP-UHFFFAOYSA-N 0.000 description 2
RDCFVGPXAHCPPY-UHFFFAOYSA-N pyrazine;dihydrochloride Chemical compound Cl.Cl.C1=CN=CC=N1 RDCFVGPXAHCPPY-UHFFFAOYSA-N 0.000 description 2
HVQTUKRBUPPQFO-UHFFFAOYSA-N pyrrolo[1,2-a]thieno[3,2-e]pyrazin-5(4h)-one Chemical compound N12C=CC=C2C(=O)NC2=C1SC=C2 HVQTUKRBUPPQFO-UHFFFAOYSA-N 0.000 description 2
XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
230000011514 reflex Effects 0.000 description 2
230000033764 rhythmic process Effects 0.000 description 2
229940076279 serotonin Drugs 0.000 description 2
239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 2
238000004611 spectroscopical analysis Methods 0.000 description 2
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
XREXPQGDOPQPAH-QKUPJAQQSA-K trisodium;[(z)-18-[1,3-bis[[(z)-12-sulfonatooxyoctadec-9-enoyl]oxy]propan-2-yloxy]-18-oxooctadec-9-en-7-yl] sulfate Chemical compound [Na+].[Na+].[Na+].CCCCCCC(OS([O-])(=O)=O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(CCCCCC)OS([O-])(=O)=O)COC(=O)CCCCCCC\C=C/CC(CCCCCC)OS([O-])(=O)=O XREXPQGDOPQPAH-QKUPJAQQSA-K 0.000 description 2
229940100445 wheat starch Drugs 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
UZKBSZSTDQSMDR-UHFFFAOYSA-N 1-[(4-chlorophenyl)-phenylmethyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)N1CCNCC1 UZKBSZSTDQSMDR-UHFFFAOYSA-N 0.000 description 1
IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 1
GFISDBXSWQMOND-UHFFFAOYSA-N 2,5-dimethoxyoxolane Chemical compound COC1CCC(OC)O1 GFISDBXSWQMOND-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
WYWNEDARFVJQSG-UHFFFAOYSA-N 2-methylserotonin Chemical compound C1=C(O)C=C2C(CCN)=C(C)NC2=C1 WYWNEDARFVJQSG-UHFFFAOYSA-N 0.000 description 1
KYBCXTTWIOZBNR-UHFFFAOYSA-N 2-piperazin-1-yl-1-pyrrolidin-1-ylethanone Chemical compound C1CCCN1C(=O)CN1CCNCC1 KYBCXTTWIOZBNR-UHFFFAOYSA-N 0.000 description 1
VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 1
TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
XGAFCCUNHIMIRV-UHFFFAOYSA-N 4-chloropyridine;hydron;chloride Chemical compound Cl.ClC1=CC=NC=C1 XGAFCCUNHIMIRV-UHFFFAOYSA-N 0.000 description 1
ROMLJLJHWULIPT-UHFFFAOYSA-N 4-phenyl-5-thia-1,7-diazatricyclo[7.3.0.02,6]dodeca-2(6),3,9,11-tetraen-8-one Chemical compound C=1C=2N3C=CC=C3C(=O)NC=2SC=1C1=CC=CC=C1 ROMLJLJHWULIPT-UHFFFAOYSA-N 0.000 description 1
102000056834 5-HT2 Serotonin Receptors Human genes 0.000 description 1
108091005479 5-HT2 receptors Proteins 0.000 description 1
HAFMRZOKMBAZMK-UHFFFAOYSA-N 5-phenyl-3-pyrrol-1-ylthiophene-2-carbonyl azide Chemical compound [N-]=[N+]=NC(=O)C=1SC(C=2C=CC=CC=2)=CC=1N1C=CC=C1 HAFMRZOKMBAZMK-UHFFFAOYSA-N 0.000 description 1
ACJDDOYOEDXGKX-UHFFFAOYSA-N 8-(1,4-diazepan-1-yl)-3-thia-1,7-diazatricyclo[7.3.0.02,6]dodeca-2(6),4,7,9,11-pentaene Chemical compound C1CCNCCN1C(C1=CC=CN11)=NC2=C1SC=C2 ACJDDOYOEDXGKX-UHFFFAOYSA-N 0.000 description 1
ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-N 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
AJDOQRMVWOJFCG-UHFFFAOYSA-N Cl.FC(C=1C=C(C=CC1)N1CCN(CC1)C=1C=2N(C3=C(N1)C=CS3)C=CC2)(F)F Chemical compound Cl.FC(C=1C=C(C=CC1)N1CCN(CC1)C=1C=2N(C3=C(N1)C=CS3)C=CC2)(F)F AJDOQRMVWOJFCG-UHFFFAOYSA-N 0.000 description 1
208000032612 Glial tumor Diseases 0.000 description 1
206010018338 Glioma Diseases 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
101000830713 Homo sapiens Torsin-3A Proteins 0.000 description 1
UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
229930182816 L-glutamine Natural products 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
JLVHTNZNKOSCNB-YSVLISHTSA-N Mesulergine Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NS(=O)(=O)N(C)C)=C3C2=CN(C)C3=C1 JLVHTNZNKOSCNB-YSVLISHTSA-N 0.000 description 1
PGBFYLVIMDQYMS-UHFFFAOYSA-N Methyl thiophene-2-carboxylate Chemical class COC(=O)C1=CC=CS1 PGBFYLVIMDQYMS-UHFFFAOYSA-N 0.000 description 1
206010029260 Neuroblastoma Diseases 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 1
102100024603 Torsin-3A Human genes 0.000 description 1
241000009298 Trigla lyra Species 0.000 description 1
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
229960003896 aminopterin Drugs 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
210000000702 aorta abdominal Anatomy 0.000 description 1
210000003818 area postrema Anatomy 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
230000036471 bradycardia Effects 0.000 description 1
230000000059 bradycardiac effect Effects 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
244000309466 calf Species 0.000 description 1
239000002775 capsule Substances 0.000 description 1
LBCCJNLNXBZJDX-UHFFFAOYSA-N chembl293219 Chemical compound FC(F)(F)C1=CC=CC(N2CCN(CC2)C=2C3=CC=CN3C=3SC(=CC=3N=2)C=2C=CC=CC=2)=C1 LBCCJNLNXBZJDX-UHFFFAOYSA-N 0.000 description 1
CMBPNOCCPKFOHS-UHFFFAOYSA-N chembl302225 Chemical compound C1CN(C)CCN1C(C1=CC=CN11)=NC2=C1C=CS2 CMBPNOCCPKFOHS-UHFFFAOYSA-N 0.000 description 1
QYWDOJXSLBBWLE-UHFFFAOYSA-N chembl54720 Chemical compound C1CN(C=2C3=CC=CN3C=3SC=CC=3N=2)CCN1CC1=CC=CC=C1 QYWDOJXSLBBWLE-UHFFFAOYSA-N 0.000 description 1
DYFVORIBDGMRNZ-UHFFFAOYSA-N chembl62445 Chemical compound C1CNCCN1C(C1=CC=CN11)=NC2=C1SC(C=1C=CC=CC=1)=C2 DYFVORIBDGMRNZ-UHFFFAOYSA-N 0.000 description 1
BKNVUCYNQODGLA-UHFFFAOYSA-N chembl62612 Chemical compound CC1=C(C)SC(N2C=CC=C22)=C1N=C2N(CC1)CCN1CC1=CC=CC=C1 BKNVUCYNQODGLA-UHFFFAOYSA-N 0.000 description 1
DLRDSROWZPGGDS-UHFFFAOYSA-N chembl63289 Chemical compound C1CN(C(=O)OCC)CCN1C(C1=CC=CN11)=NC2=C1SC=C2 DLRDSROWZPGGDS-UHFFFAOYSA-N 0.000 description 1
HGYNWZFKHCMJGM-UHFFFAOYSA-N chembl63845 Chemical compound FC(F)(F)C1=CC=CC(N2CCN(CC2)C=2C3=CC=CN3C=3C=CSC=3N=2)=C1 HGYNWZFKHCMJGM-UHFFFAOYSA-N 0.000 description 1
VFBDQDRLYCWTOU-UHFFFAOYSA-N chembl64559 Chemical compound FC(F)(F)C1=CC=CC(N2CCN(CC2)C=2C3=CC=CN3C=3C=C(SC=3N=2)C=2C=CC=CC=2)=C1 VFBDQDRLYCWTOU-UHFFFAOYSA-N 0.000 description 1
DRJDHULKURBTLQ-UHFFFAOYSA-N chembl65669 Chemical compound C1CN(C)CCN1C(C1=CC=CN11)=NC2=C1C=C(C=1C=CC=CC=1)S2 DRJDHULKURBTLQ-UHFFFAOYSA-N 0.000 description 1
UOPMUBWAOQBXJF-UHFFFAOYSA-N chembl68390 Chemical compound FC(F)(F)C1=CC=CC(N2CCN(CC2)C=2C3=CC=CN3C=3SC=CC=3N=2)=C1 UOPMUBWAOQBXJF-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical class C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
239000006071 cream Substances 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
239000006196 drop Substances 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
ZFAMIEOHFQQWDA-UHFFFAOYSA-N ethyl 4-(4-phenyl-3-thia-1,7-diazatricyclo[7.3.0.02,6]dodeca-2(6),4,7,9,11-pentaen-8-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(C1=CC=CN11)=NC2=C1SC(C=1C=CC=CC=1)=C2 ZFAMIEOHFQQWDA-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
210000001105 femoral artery Anatomy 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
230000007154 intracellular accumulation Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229950008693 mesulergine Drugs 0.000 description 1
CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
FYNQCKPHPLFYDN-UHFFFAOYSA-N methyl 3-pyrrol-1-ylthiophene-2-carboxylate Chemical compound S1C=CC(N2C=CC=C2)=C1C(=O)OC FYNQCKPHPLFYDN-UHFFFAOYSA-N 0.000 description 1
239000007923 nasal drop Substances 0.000 description 1
229940100662 nasal drops Drugs 0.000 description 1
ZHCAAFJSYLFLPX-UHFFFAOYSA-N nitrocyclohexatriene Chemical class [O-][N+](=O)C1=CC=C=C[CH]1 ZHCAAFJSYLFLPX-UHFFFAOYSA-N 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000002831 pharmacologic agent Substances 0.000 description 1
239000000843 powder Substances 0.000 description 1
SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
HYHBKLWDTGTBME-UHFFFAOYSA-N pyrazin-1-ium;chloride Chemical compound Cl.C1=CN=CC=N1 HYHBKLWDTGTBME-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
210000003752 saphenous vein Anatomy 0.000 description 1
239000000198 serotonin 5-HT3 receptor agonist Substances 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
239000006190 sub-lingual tablet Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
229940113082 thymine Drugs 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
230000001515 vagal effect Effects 0.000 description 1
239000011534 wash buffer Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Animal Behavior & Ethology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Neurology (AREA)
General Health & Medical Sciences (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Anesthesiology (AREA)
Otolaryngology (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

NZ247791A 1992-06-05 1993-06-04 Pyrrolothienopyrazine derivatives, their preparation and pharmaceutical compositions NZ247791A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
FR9206800A FR2691967B1 (fr)	1992-06-05	1992-06-05	Nouveaux composes pyrrolothienopyraziniques, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent.

Publications (1)

Publication Number	Publication Date
NZ247791A true NZ247791A (en)	1994-12-22

Family

ID=9430449

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NZ247791A NZ247791A (en)	1992-06-05	1993-06-04	Pyrrolothienopyrazine derivatives, their preparation and pharmaceutical compositions

Country Status (11)

Country	Link
EP (1)	EP0573360B1 (de)
JP (1)	JPH0794460B2 (de)
AT (1)	ATE170187T1 (de)
AU (1)	AU659738B2 (de)
CA (1)	CA2097779A1 (de)
DE (1)	DE69320542T2 (de)
DK (1)	DK0573360T3 (de)
ES (1)	ES2123038T3 (de)
FR (1)	FR2691967B1 (de)
NZ (1)	NZ247791A (de)
ZA (1)	ZA933942B (de)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP3268003B1 (de) *	2015-03-12	2020-07-29	Merck Sharp & Dohme Corp.	Thienopyrazininhibitoren der irak4-aktivität

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4997433A (en) *	1990-01-16	1991-03-05	Marlowe Goble E	Endosteal fixation stud and system
FR2659332B1 (fr) *	1990-03-08	1994-04-29	Adit Et Cie	Nouvelles pyrrolo [1,2-a] thieno [3,2-f] diazepines [1,4], leur procede de preparation et les compositions pharmaceutiques qui les contiennent.
FR2660310B1 (fr) *	1990-03-27	1992-06-05	Adir	Nouveaux derives de la 4h-pyrrolo[1,2a] thieno[2,3-f] diazepine[1,4], leur procede de preparation et les compositions pharmaceutiques les renfermant.

1992
- 1992-06-05 FR FR9206800A patent/FR2691967B1/fr not_active Expired - Fee Related
1993
- 1993-06-03 DK DK93401416T patent/DK0573360T3/da active
- 1993-06-03 EP EP93401416A patent/EP0573360B1/de not_active Expired - Lifetime
- 1993-06-03 AT AT93401416T patent/ATE170187T1/de not_active IP Right Cessation
- 1993-06-03 DE DE69320542T patent/DE69320542T2/de not_active Expired - Fee Related
- 1993-06-03 ES ES93401416T patent/ES2123038T3/es not_active Expired - Lifetime
- 1993-06-04 ZA ZA933942A patent/ZA933942B/xx unknown
- 1993-06-04 CA CA002097779A patent/CA2097779A1/fr not_active Abandoned
- 1993-06-04 AU AU40059/93A patent/AU659738B2/en not_active Ceased
- 1993-06-04 JP JP5134922A patent/JPH0794460B2/ja not_active Expired - Lifetime
- 1993-06-04 NZ NZ247791A patent/NZ247791A/en unknown

Also Published As

Publication number	Publication date
DK0573360T3 (da)	1999-05-25
ES2123038T3 (es)	1999-01-01
FR2691967B1 (fr)	1995-06-09
JPH06172363A (ja)	1994-06-21
JPH0794460B2 (ja)	1995-10-11
EP0573360B1 (de)	1998-08-26
ZA933942B (en)	1993-12-30
AU659738B2 (en)	1995-05-25
CA2097779A1 (fr)	1993-12-06
DE69320542D1 (de)	1998-10-01
FR2691967A1 (fr)	1993-12-10
DE69320542T2 (de)	1999-04-29
EP0573360A1 (de)	1993-12-08
AU4005993A (en)	1993-12-09
ATE170187T1 (de)	1998-09-15

Publication	Publication Date	Title
US5159083A (en)	1992-10-27	Certain aminomethyl phenylimidazole derivatives; a class of dopamine receptor subtype specific ligands
AU665366B2 (en)	1996-01-04	Benzimidazolone derivatives as 5-HT1A and 5-HT2 antagonists
US5478934A (en)	1995-12-26	Certain 1-substituted aminomethyl imidazole and pyrrole derivatives: novel dopamine receptor subtype specific ligands
JP3057109B2 (ja)	2000-06-26	新規インドール誘導体
CA3038280A1 (en)	2017-04-06	Heteroaryl derivatives as sepiapterin reductase inhibitors
HU208132B (en)	1993-08-30	Process for producing 3-arylcarbonyl-1h-indole derivatives and pharmaceutical compositions comprising same
CZ288944B6 (cs)	2001-10-17	Derivát 5H-thiazolo[3,2-a]pyrimidinu, způsob jeho přípravy, meziprodukt pro jeho přípravu a farmaceutický prostředek, který ho obsahuje
EA027752B1 (ru)	2017-08-31	Терапевтически активные производные пиразолопиримидина
ES2269822T3 (es)	2007-04-01	Derivados de pirazol de anillos fusionados.
NZ215616A (en)	1990-01-29	Pyridazinone derivatives and pharmaceutical compositions
FI67550B (fi)	1984-12-31	Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 2,10-dihydro-4-piperazinyl-pyrazolo(3,4-b)(1,5)bensodiazepinderivat
US6586422B2 (en)	2003-07-01	Pyrazine and triazine derivatives of 1,2,4,5-tetrahydro-Benzo or Thieno [d] azepine
US5599812A (en)	1997-02-04	Tricyclic pyrrolopyrazine 5-HT3 -active compounds
CZ290678B6 (cs)	2002-09-11	3-Substituované 3,4,5,7-tetrahydropyrrolo[3´,4´: 4,5]thieno[2,3-d]pyrimidinové deriváty, způsob jejich přípravy a použití
NZ247791A (en)	1994-12-22	Pyrrolothienopyrazine derivatives, their preparation and pharmaceutical compositions
NZ280734A (en)	1997-09-22	Thieno[2,3-d]pyrrolo[1,2-a]pyrrole, thieno[3,2-d]-pyrrolo[1,2-a]pyrrole, and pyrrolo[1,2-a]indole derivatives
JPH09508637A (ja)	1997-09-02	５ｈｔ２ｂレセプタ拮抗薬縮合インドール
JPS62135475A (ja)	1987-06-18	２−置換−ｅ−融合−〔１，２，４〕トリアゾロ−〔１，５−Ｃ〕ピリミジン
US5371080A (en)	1994-12-06	Imidazoquinazoline compounds and their use
HU211588A9 (en)	1995-12-28	Piperazine derivatives
US6002005A (en)	1999-12-14	Certain 1-substituted aminomethyl imidazole and pyrrole derivatives: novel dopamine receptor subtype specific ligands
EP0118205A1 (de)	1984-09-12	(5-(2-Aminomethyl-imidazol-1-yl)-1,3-dialkyl-1h-pyrazol-4-yl)(aryl)Methanone und Verfahren zu deren Herstellung
JPH05163278A (ja)	1993-06-29	三環に置換基を有するテトラヒドロピリジン誘導体
MXPA06009179A (es)	2006-12-13	Moduladores de receptores selectivos del subtipo gaba-a heterociclicos

Legal Events

Date	Code	Title	Description
2002-06-28	ASS	Change of ownership	Owner name: LES LABORATOIRES SERVIER, FR Free format text: OLD OWNER(S): ADIR ET COMPAGNIE

Date

Code

Title

Description

2002-06-28

ASS

Change of ownership

Owner name: LES LABORATOIRES SERVIER, FR

Free format text: OLD OWNER(S): ADIR ET COMPAGNIE